The catabolism of glutathione occurs through an inter-organ process which involves release from various tissues, transport via the plasma and hydrolysis which occurs primarily in the kidney. The kidney extracts 80-95% of the plasma glutathione in a single pass. Renal catabolism of glutathione is carried out by Gamma-glutamyltranspeptidase and either of two peptidase activities that are also associated with the lumenal surface of the renal brush border membrane. The rapid turnover of renal gluthathione involves its initial secretion from the proximal tubbule cells into the tubular lumen. The specific aims of this proposal are to further characterize the hydrophobic domain of the Gamma-glutamyltranspeptidase, to determine the relative contribution of the two peptidase activities to the hydrolysis of cysteinylglycine, to characterize the mechanism of renal extraction of glutathione, to quantitate the process of glutathione secretion and to investigate the physiological function of the turnover of renal glutathione.